Structure and function of the cystic fibrosis transmembrane conductance regulator

Cystic fibrosis (CF) is a lethal autosomal recessive genetic disease caused by mutations in the CF transmembrane conductance regulator (CFTR). Mutations in the CFTR gene may result in a defective processing of its protein and alter the function and regulation of this channel. Mutations are associated with different symptoms, including pancreatic insufficiency, bile duct obstruction, infertility in males, high sweat Cl-, intestinal obstruction, nasal polyp formation, chronic sinusitis, mucus dehydration, and chronic Pseudomonas aeruginosa and Staphylococcus aureus lung infection, responsible for 90% of the mortality of CF patients. The gene responsible for the cellular defect in CF was cloned in 1989 and its protein product CFTR is activated by an increase of intracellular cAMP. The CFTR contains two membrane domains, each with six transmembrane domain segments, two nucleotide-binding domains (NBDs), and a cytoplasmic domain. In this review we discuss the studies that have correlated the role of each CFTR domain in the protein function as a chloride channel and as a regulator of the outwardly rectifying Cl- channels (ORCCs)

Results in the treatment of paralytic calcaneus-valgus feet with the Westin technique

Between 1988 and 2003, 23 patients with paralytic calcaneus-valgus feet were submitted to the Westin procedure and 17 patients (25 feet) were re-evaluated. Nine patients were male and eight were female. The mean age at the surgical procedure was 8±5 years. The aetiology of paralysis was sequelae of poliomyelitis in 6 patients (8 feet) and of myelomeningocele in 11 patients (17 feet). The mean follow-up period was 6±6 years. The results were analysed clinically and radiographically considering the decrease of the retropulsion, the patient’s satisfaction, and the increase of the lateral tibiocalcaneal angle. Results were considered satisfactory when the patients showed a decrease of the retropulsion during gait, improvement of the gait pattern, and an increase of the tibiocalcaneal angle. As an overall result, 16 patients (94.2%) were satisfied and 1 patient (two feet) dissatisfied with the outcome. The increase of the tibiocalcaneal angle was significant for the myelomeningocele patients (P=0.001), but not for poliomyelitis (P=0.053). No statistical relation between the follow-up period and the increase of the tibiocalcaneal angle was found (r=0.04). The authors concluded that the Westin procedure is a good technique for the treatment of paralytic calcaneus valgus feet with myelomeningocele